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Studies on integrinα3β1-mediated signaling

整合素α3β1介导的信号传导研究

基本信息

批准号：
14580697
负责人：
GU Jianguo
金额：
$ 2.3万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580697/
关键词：
basement membrane integrin laminin phosphotyrosine matrix metallonroteinase signal N-glycan 糖鎖

项目摘要

The α3β1 integrin-mediated signaling events triggered by cell adhesion to laminin-10/11(LN-10/11) are quite different from those triggered by adhesion to fibronectin (FN). LN-10/11 preferentially activates Rac, but not Rho, through an α3β1 integrin-dependent pathway involving a p130Cas-CrkII-DOCK18O complex, thereby strongly promoting cell migration through enhanced formation of lamellipodia. On the other hand, the intracellular signaling pathways regulating cell survival focusing on two distinct signaling pathways involving PI 3-kinase/Akt and MEKi/ERK have been investigated. LN-10/11 is more potent than FN in suppressing apoptosis induced by serum deprivations The anti-apoptotic effects of LN-10I11 could be inhibited by the PI 3-kinase inhibitor wortmannin, whereas the anti-apoptotic effects of FN were inhibited by the MEKi inhibitor PD98059. Our results provide clear evidence that different signaling pathways leading to cell survival are activated, on different ECM ligands. Furthermore, remodeling of N-glycans of the integrin could also modulate its ligand binding and integrin-mediated signaling. Since laminins are the major components of the basement membrane of epithelium, our work supports the notion that a function of the basement membrane is to provide distinctive cell survival signals for establishment and maintenance of epithelial tissue.

由细胞粘附于层粘连蛋白10/11（LN-10/11）所触发的α3β1整合素介导的信号传导事件与由粘附于纤连蛋白（FN）所触发的信号传导事件是完全不同的。LN-10/11通过涉及p130 Cas-CrkII-DOCK 18 O复合物的α3β1整联蛋白依赖性途径优先激活Rac，但不激活Rho，从而通过增强板状伪足的形成强烈促进细胞迁移。另一方面，调节细胞存活的细胞内信号通路集中于涉及PI 3-激酶/Akt和MEKi/ERK的两种不同的信号通路已被研究。LN-10/11在抑制血清剥夺诱导的细胞凋亡方面比FN更有效。LN-10/11的抗细胞凋亡作用可被PI 3-激酶抑制剂渥曼青霉素抑制，而FN的抗细胞凋亡作用可被MEKi抑制剂PD 98059抑制。我们的研究结果提供了明确的证据表明，不同的ECM配体激活了导致细胞存活的不同信号通路。此外，整合素的N-聚糖的重塑也可以调节其配体结合和整合素介导的信号传导。由于层粘连蛋白是上皮基底膜的主要成分，我们的工作支持这样的概念，即基底膜的功能是提供独特的细胞存活信号，用于上皮组织的建立和维持。

项目成果

期刊论文数量（48）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Isaji, T., gu, J., Nishiuchi, R., Zhao, Y, Takahashi, M., Miyoshi, E., Honke, K., Sekiguchi, K., Taniguchi, N.: "Introduction of bisecting GlcNAc into integrin α5β1 reduces ligand binding and down-regulates cell adhesion and cell migration."J.Biol.Chem. 2

Isaji, T.、gu, J.、Nishiuchi, R.、Zhao, Y、Takahashi, M.、Miyoshi, E.、Honke, K.、Sekiguchi, K.、Taniguchi, N.：“将 GlcNAc 等分引入整合素 α5β1 减少配体结合并下调细胞粘附和细胞迁移。”J.Biol.Chem. 2